Abstract | INTRODUCTION: METHODS: For precursor synthesis, a 4-step synthesis starting from N-phenyl- o-phenylenediamine was set up. Radiosynthesis was established and optimized using standard methods and subsequently automated in a GE TRACERlabFx C Pro synthesizer. Preclinical testing was performed comprising affinity and selectivity testing on human membranes as well as stability and blood-brain-barrier-penetration using in-vitro models. RESULTS: Precursor molecule (APPI:0) and reference compound ( Me@APPI) were synthesized with 26.5% and 21.4% overall yield, respectively. So far, 1.25±0.72 GBq [(11)C] Me@APPI with 54.35±7.80 GBq/μmol specific activity were produced (n=11). Affinity of reference compounds was determined as 8.08±1.75 nM for Me@APPI and 19.31±2.91 nM for APPI:0, respectively (n≥9). IAM-chromatography experiments (n=3) revealed a P(m) value of 1.51±0.34 for Me@APPI. Stability testing using human liver microsomes revealed that 99.5% of the tracer was found to be still intact after 60 minutes (n=4). CONCLUSION: Present data indicate that [(11)C] Me@APPI has promising properties to become a clinically useful NET-PET-tracer. Further in-vitro and in-vivo evaluations are currently under way.
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Authors | Christina Mark, Birgit Bornatowicz, Markus Mitterhauser, Matthias Hendl, Lukas Nics, Daniela Haeusler, Rupert Lanzenberger, Michael L Berger, Helmut Spreitzer, Wolfgang Wadsak |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 40
Issue 2
Pg. 295-303
(Feb 2013)
ISSN: 1872-9614 [Electronic] United States |
PMID | 23265665
(Publication Type: Journal Article)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1H-benzo(d)imidazol-2(3H)-one
- Benzimidazoles
- Carbon Radioisotopes
- Norepinephrine Plasma Membrane Transport Proteins
- benzimidazole
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Topics |
- Automation
- Benzimidazoles
(chemistry, metabolism)
- Blood-Brain Barrier
(metabolism)
- Carbon Radioisotopes
- Drug Stability
- Humans
- Isotope Labeling
- Norepinephrine Plasma Membrane Transport Proteins
(metabolism)
- Positron-Emission Tomography
(methods)
- Quality Control
- Radiochemistry
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